P1708: PREGNANCIES IN YOUNG ADULTS WITH A HISTORY OF ACUTE LYMPHOBLASTIC LEUKEMIA IN ITALY. A CAMPUS ALL SURVEY.
Authors: F. Giglio, A. Bruno, C. Papayannidis, M. Dargenio, M. Cerrano, F. Forghieri, M. Fumagalli, M. Lunghi, M. Annunziata, M. Bonifacio, F. Ferrara, F. Ciceri, G. Pizzolo, A. Vitale, R. Foà
Journal: HemaSphere (2022)

Background: Survival after acute lymphoblastic leukemia (ALL) has greatly improved in the last 20 years, particularly in children, adolescents and young adults (AYA). Fertility impairments are among the main concerns for the long-term survivors. Few studies have focused on fertility issues within this selected population and the existing data are difficult to interpret due to different treatment regimens, small sample sizes and unavailability of data concerning fertility issues such as pregnancies in many Centers. Overall, fertility outcomes seem to be comparable between childhood ALL survivors and controls, except for a higher proportion of miscarriages, but very little is known for adult survivors. Aims: Register fertility outcomes of male and female adult ALL long-term survivors. Methods: We conducted a survey within the Italian Campus ALL group about pregnancies in adult ALL survivors. Seventeen centers responded, accounting for 803 AYA patients (489 males, 315 females) treated between 2005 and 2020. All country geographic areas were represented. Our survey consisted in a first questionnaire concerning patients, disease characteristics and treatments including allogeneic stem cell transplant (allo-HSCT). A second questionnaire was specific on conception and pregnancies such as use of medical help to become pregnant and pregnancy outcomes (positive or negative such as birth defects, miscarriages, medical abortions or stillbirths). Results: Ten out of 17 centers referred pregnancies. We registered 31 pregnancies in 11 female and 14 male patients (median age at ALL diagnosis 24 years; range 16-38). All patients had received chemotherapy (pediatric-like in half of the patients), while 9 patients received also allo-HSCT. 15 patients were diagnosed with B-lineage ALL, 7 with T-ALL, 3 with Ph+ ALL. 27 children were naturally conceived, while medical help was necessary for 4 pregnancies. Only 2 pregnancies were achieved through cryopreserved gametes (all male patients). The median age at the time of the delivery was 33 years (range 25-46), with a median time from the diagnosis of ALL of 9 years. We registered 6 patients having 2 children and 2 patients having twin pregnancies (1 complicated with the death of one foetus). The incidence of pregnancy diseases and birth defects was low: 1 pregnancy was complicated by diabetes, 1 with neonatal jaundice, 1 with urethral obstruction necessitating surgical correction at birth. Summary/Conclusion: Our survey shows that pregnancies in AYA ALL survivors are fairly uncommon but possible, even after allo-HSCT. The major limit of the study is the selection bias related to missing information in most centers about pregnancies and even more about miscarriages and medical abortions (none were registered). Most pregnancies were uncomplicated and we didn’t document a high incidence of pregnancy-related diseases or birth defects. Interestingly, only a small fraction of pregnancies were carried out with medical help or cryopreserved gametes. More efforts are needed in both patients’ information and medical care to improve fertility rates in AYA ALL survivors, particularly as the survival rates are improving. Having more precise data about fertility is of paramount importance to give better information about gametotoxicity in newly diagnosed patients. Fertility issues and pregnancies should become part of the medical follow-up, considering the higher rates of survival and even more with the possibility of new chemo-free approaches. The institution of specific national guidelines/recommendations is needed to promote this cultural shift.